Molecular mechanism of cancer chemoprevention by anthocyanins

花青素化学预防癌症的分子机制

基本信息

批准号：
13660130
负责人：
HOU De-xing
金额：
$ 2.24万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

Anthocyanidins are the aglycon nucleuses of anthocyanins, which are reddish pigments widely spread in colored fruits and vegetables. To investigate the anti-cancer effect of anthocyanins, induction of apoptosis was tested in human promyelocytic leukemia cells (HL-60), which is a valid model for testing antileukemic or general antitumoral compounds. Of six anthocyanidins representing the aglycons of most of anthocyanins, only those with an ortho-dihydroxyphenyl structure on the B-ring induce apoptosis, suggesting that the ortho-dihydroxyphenyl structure of anthocyanidins may contribute to the induction of apoptosis. Delphinidin, the most potent inducer, causes apoptosis in a time-and dose-dependent manner. The efficacious induction of apoptosis was observed at 100 μM for 6 h. Concomitant with the apoptosis, delphinidin stimulates JNK pathway activation including JNK phosphorylation and c-jun gene expression, and activates caspase-3. Antioxidants including N-acetyl-L-cysteine (NAC) and catalase effectively block delphinidin-induced JNK phosphorylation, caspase-3 activation, and DNA fragmentation. Moreover, anthocyanidins directly cause HL-60 cells to generate intracellular hydrogen peroxide. Thus, anthocyanidins may trigger an apoptotic death program through an oxidative stress-involved JNK signaling pathway. The induction of apoptosis by anthocyanins may be the pivotal mechanism by which its chemopreventive action against cancer is based.

花色苷是花色苷的核核，它们是红色的色素广泛散布在有色水果和蔬菜中。为了研究花色苷的抗癌作用，在人类临床细胞性白血病细胞（HL-60）中测试了细胞凋亡的诱导，这是测试抗无菌或一般抗肿瘤化合物的有效模型。在六粒花色苷中代表了大多数花色苷的aglycons，只有在B形环上具有正二羟基苯基结构的aglycons诱导细胞凋亡，这表明正常二羟基苯基苯基结构可能有助于凋亡诱导的凋亡诱导。 Delphinidin是最有效的诱导素，以时间依赖性的方式引起凋亡。在100μM下观察到凋亡的有效诱导6小时。与细胞凋亡相关，Delphinidin刺激JNK途径激活，包括JNK磷酸化和C-Jun基因表达，并激活caspase-3。包括N-乙酰L-半胱氨酸（NAC）和过氧化氢酶在内的抗氧化剂有效阻断Delphinidin诱导的JNK磷酸化，caspase-3激活和DNA片段化。此外，花青素直接导致HL-60细胞产生细胞内氢过氧化氢。那就是花青素可以通过氧化应激的JNK信号通路触发凋亡死亡程序。花色苷诱导凋亡可能是其对癌症的化学预防作用的关键机制。